Ultraviolet (UV) light affects the neurosensory system of the skin which likely plays an important pathophysiological role in various skin diseases. Mediators released from the cutaneous neurosensory system by UV irradiation participate in the sunburn reaction and UV-induced immunosupression, and in some skin diseases (e.g. psoriasis) the therapeutic effectiveness of UV treatment may be mediated by the cutaneous neurosensory system. This proposal will investigate the effect of UV light on the neurosensory system by measuring regulation of a number of soluble mediators released in response to UV irradiation. We will use cultured dorsal root ganglia (DRG) as a model of the peripheral nervous system (PNS) to investigate direct effects of UV light on sensory nerve fibers and their respective cell bodies. Responses measured in DRG will be compared to those in the intact neurocutaneous system in hairless mice. In Aim 1 we will analyze the effects of broadband and narrowband UVB irradiation on the sensory nerves from DRG. After single or repeated UVB exposure of DRG we will assess the UV effects on (i) the neuropeptides calcitonin gene-related peptide and substance P, (ii) the intracellular calcium levels of axons and ganglia cells, (iii) the expression of c-fos as a marker of neuronal activation, and (iv) the pattern and speed of axonal outgrowth. In Aim 2 we will compare the acute and chronic UV-induced effects observed in our "DRG-in vitro model" with the effects of acute and chronic UVB exposure on sensory nerves in the skin as well as on their respective cell bodies in the DRKs in hairless mice. The comparison of in vitro and in vivo data from our experiments should give us new insight in the effects of UV light on the cutaneous neurosensory system, and increase our understanding of direct and indirect interactions between UV irradiation and cutaneous nerves. In the future this knowledge could result in the improvement of present and the development of new treatments for skin diseases with neurosensory components.